Role of Oleic Acid in the Gut-Liver Axis: From Diet to the Regulation of Its Synthesis via Stearoyl-CoA Desaturase 1 (SCD1)

Abstract

The consumption of an olive oil rich diet has been associated with the diminished incidence of cardiovascular disease and cancer. Several studies have attributed these beneficial effects to oleic acid (C18 n-9), the predominant fatty acid principal component of olive oil. Oleic acid is not an essential fatty acid since it can be endogenously synthesized in humans. Stearoyl-CoA desaturase 1 (SCD1) is the enzyme responsible for oleic acid production and, more generally, for the synthesis of monounsaturated fatty acids (MUFA). The saturated to monounsaturated fatty acid ratio affects the regulation of cell growth and differentiation, and alteration in this ratio has been implicated in a variety of diseases, such as liver dysfunction and intestinal inflammation. In this review, we discuss our current understanding of the impact of gene-nutrient interactions in liver and gut diseases, by taking advantage of the role of SCD1 and its product oleic acid in the modulation of different hepatic and intestinal metabolic pathways.

Keywords: MUFA; gut; liver; oleic acid; olive oil; stearoyl-CoA desaturase.

Figure 1

Scheme representing the biosynthesis of MUFA in animals. Stearoyl CoA Desaturase 1 (SCD1) catalyzes the rate-limiting step for the conversion of saturated fatty acid (SFA) into monounsaturated ones (MUFA). (ACC—acetyl CoA carboxylase; FASN—fatty acid synthase; ELOVL6—fatty acid elongases 6).

Figure 2

A theoretical model of metabolic control of lipogenesis by SCD1 in cancer cells. SCD1—stearoyl-CoA desaturase 1; ACC—acetyl-CoA carboxylase; AMPK—AMP-activated kinase; MUFA—monounsaturated fatty acids; SFA—saturated fatty acids.

Figure 3

SCD1 inhibition in non-alcholic fatty liver disease (NAFLD). Different methodologies have been used to suppress the stearoyl CoA desaturase 1 (SCD1) activity in the liver, ranging from tissue specific mouse model (LSCD1KO) to Asebia mice, homozygous for naturally occurred mutation which result in the lack of SCD1, to specific inhibitor or antisense oligonucleotide (ASO). At the same time, different disease models have been employed to dissect the role of SCD1 in hepatic disorders. The main one consisted in diet administration, such as a high fat diet (HFD), high carbohydrates diet (HCD) and methionine-choline deficient diet (MCD). The hepatic suppression of SCD1 expression resulted in an altered saturated (SFA) to monounsaturated fatty acid (MUFA) ratio, with the concomitant decreased de novo lipogenesis programs and increased fatty acids β-oxidation pathways. Although these animals are protected from liver steatosis, they normally display liver injury, which is promptly rescued by oleic acid endogenous (from other tissues, such as intestine or white adipose tissue) or exogenous (from diet) supplementation.

Figure 4

SCD1 inhibition in gut disorders. stearoyl CoA desaturase 1 (SCD1) suppression in intestinal cells offers a divergent scenario. Studies conducted in cancer cell lines indicated that SCD1 suppression inhibits tumor growth by increasing mitochondrial dysfunction and reactive oxygen species (ROS) accumulation. On the other side, investigations carried out using mouse models, demonstrated that the loss of SCD1 promotes an inflammatory state that worsens inflammatory bowel disease (IBD) as well as cancer growth and progression. Intriguingly, the consumption of oleic acid enriched diet reverses the disease phenotype.